This invention relates to a method of assessing the integrity of the visual field by objective elecrophysiological recording with simultaneous multifocal stimulation using different stimulus sequences for each part of the field. In particular, it relates to a method for accurately diagnosing and assessing the extent of visual field loss in a glaucoma patient or any other neuro-ophthalmic disorders where there is loss of peripheral vision. It provides for more rapid collection and assessment of data during the recording than any pre-existing technology.
In determining the extent of damage to the visual system in ocular diseases such as glaucoma, investigation of the visual field (peripheral vision) is vital. Until recently this has relied on subjective psychophysical tests known as perimetry of which the most widely used is the Humphrey visual field analyser. This involves presentation of stimuli of varying luminance in different parts of the visual field to determine visual thresholds and relies on patient decisions. Perimetry therefore involves an element of uncertainty in interpretation of patient responses.
There is a strong demand for an objective measurement of the visual field, to supplement the variable performances seen in perimetry and other psychophysical tests in the evaluation of glaucomaxe2x80x94a disease which is one of the commonest causes of blindness. Recording of the electrical responses generated by the visual system in response to changing stimuli is a possible alternative. Until recently however, electrophysiological recording could only provide a summed response from the whole eye or occipital cortex, and could not assess peripheral vision.
The conventional full field visual evoked potential (VEP) provides information mostly about the central visual field. It is reported to be abnormal in about half of the population with glaucoma. Since many patients can have normal responses, this method gives poor and unreliable discriminatory power for the detection of the disease. The variable findings have previously been explained by the fact that the VEP predominantly reflects macular function and in glaucoma the damage tends to affect central vision late in the disease. With suitable recording conditions and an array of bipolar electrodes positioned overlying the visual cortex of the brain, it was shown [in Graham, Klistorner, Grigg and Billson Invest 1999 Ophthalmol Vis Sci, 40(4) ARVO abstract #318] to be possible to examine the peripheral visual field which is damaged early in glaucoma.
A major advance in stimulus and recording technology has recently been introduced which enables the presentation of a multifocal stimulus. This is now commercially available as the VERISxe2x80x94Scientific system (Electro-Diagnostic Imaging, Inc., San Francisco) or Retiscan (Roland Instruments, Wiesbaden, Germany). These systems both present a similar method for topographical analysis of recordings, and utilise the orthogonal property of different phases of a special type of binary sequence, called an m-sequence, which allows stimulation of a number of sites of the visual field simultaneously. All elements of the field are stimulated with the same m-sequence shifted in time.
Due to the long VEP response time, and possible overlap of the signal between segments, the technique as disclosed in U.S. Pat. No. 4,846,567(Sutter) requires the use of long m-sequences. The method described by Sutter does not allow the observation of responses during the recording, but only displays the product of cross-correlations at the end of the test when the entire m-sequence is finished. This property is a significant limitation since in clinical testing it is desirable to observe responses constantly during the recording procedure. In cases where the signal is unsatisfactory, recording time is wasted. In cases where the subject has a limited ability to co-operate and fixate on the screen target (eg children, elderly patients), short recording sequences are essential, as are frequent checking of the quality of each segment before it is included in the data With short recording sequences it is possible to avoid unnecessarily long recording times in cases where the signal is reliable, to stop the recording without loss of data if the patient fatigues, and allow additional runs to be added in when the response is noisy.
For example, consider the case of recording a multifocal VEP with 60 segments or 120 segments of visual field stimulated. With the method described by Sutter (above) using the same m-sequences for all segments of the visual field shifted in time, it is necessary to allow at least 500 msec, preferably 1000 msec, between segments to avoid overlap and contamination of signals. With a 75Hz frame rate at least 2250 code elements are required for 500 msec, and 4500 code elements for l000 msec. Since m-sequences only come in predefined lengths of 2nxe2x88x921, the shortest possible m-sequence required will be 2047 and 4095 elements of code respectively. This will result in recording times of approx 1 minute and 2 minutes respectively for 60 segments of visual field, 2 minutes to 4 minutes for 120 segments of field. Further increases in the number of field elements stimulated would require even greater minimum recording times before the results could be assessed in real time. Sutter alludes to the use of 255 segments or more in recording, which would be extremely useful clinically, but it would require at least 8 minutes of recording before any data could be accessed. Also, U.S. Pat. No. 5,539,482 (James and Maddess) disclosed a system whereby the contrast of each zone was modulated with a different respective temporal frequency. Each of the stimulus signals applied to each zone is orthogonal in time to the visual signals applied to all other zones such that the composition of the response into the components may be computed by Fourier transforms. The disadvantage with this method is that only a limited number of zones can be handled.
It is therefore an object of this invention to provide a method for the rapid objective measurement of the visual field based on simultaneous use of different stimulating sequences at each part of the field, where data can be readily assessed at short intervals during the recording.
In this specification and claims the following terms have the meanings as set out:
xe2x80x9cCross-correlationxe2x80x9d: Cross-correlation can be described as comparison of two sequences A=[a0, a1, . . . aNxe2x88x921] and B=[b0, b1, . . . bNxe2x88x921] to determine how much they correspond with one another. If sequence B is cyclically shifted by i elements, the cross-correlation r, can be calculated as follows       r    i    =            ∑              n        =        0                    N        -        1              ⁢                  a        n            ⁢              b                  n          -          1                    
xe2x80x9cAuto-correlationxe2x80x9d: Auto-correlation can be described as comparison of sequence A=[aO, a1, . . . aNxe2x88x921] and it""s own delayed copy to determine how much different phases of the same sequence differ one from another. If a copy of sequence A is cyclically shifted by i elements, the auto-correlation ri can be calculated as follows       r    i    =            ∑              n        =        0                    N        -        1              ⁢                  a        n            ⁢              a                  n          +          i                    
An acceptable level of cross-correlation for clinical testing is less than 6% of the auto-correlation peak (Nxe2x88x921) for a sequence of length 1023 samples or more.
xe2x80x9cM-sequencexe2x80x9d: M-sequence can be created by applying a single shift register with a number of specifically selected feedback-taps. If the shift register size is n then the length of the m-sequence is equal to 2nxe2x88x921. More detailed introduction in m-sequences can be found in MacWilliams and Sloane, xe2x80x9cPseduo-Random Sequences and Arraysxe2x80x9d, Proc IEEE, Vol 64, No 12, December 1976, pp 1715-1729.
xe2x80x9cGold family of binary sequencesxe2x80x9d: The family of the Gold sequences can be generated as a product of two m-sequences which form a xe2x80x9cpreferred pairxe2x80x9d. So called xe2x80x9cpreferred pairxe2x80x9d is a combination of m-sequences for which the cross-correlation shows only 3 different values: 1, xe2x88x922xe2x80x2m+11/2xe2x88x921, 2xe2x80x2m+11/2+1. Different members of the family may be generated by giving one of the codes a delay with respect to the other code. Information on Gold codes can be obtained from Sarwate and Pursley, xe2x80x9cCrosscorrelation Properties of Pseudorandom and Related Sequencesxe2x80x9d, Proc IEEE, Vol 68, No 5, May 1980, pp593-619.
xe2x80x9cKasami family of binary sequencesxe2x80x9d: A family of the Kasami sequences can be obtained by combining Gold codes with decimated version of one of the two m-sequences that form the Gold sequence described in the previous paragraph. Information on Kasami codes may be obtained from Sarwate and Pursley above.
The current invention attempts to address the limitations of existing systems discussed above, by using different stimulating sequences for each part of the visual field. Instead of a single m-sequence, a family of binary sequences is employed with a unique sequence for each part of the field. These sequences have low cross-correlation properties between family members and good auto-correlation properties. Ideally, the auto-correlation function of any sequence is impulse valued and cross-correlation values are zeroes for any pair of the sequences of the family. Unfortunately there is no family of binary sequences with such ideal correlation properties. For practical purposes, various families of sequences can be used such as Kasami, Gold etc. They have acceptable cross-correlation and auto-correlation properties to separate responses from different parts of visual field with sufficient accuracy. The correlation properties of Gold and Kasami families are discussed below.
Using these sequences all parts of the visual field are stimulated simultaneously according to different sequences from the family. At the completion of each recording run, which is equal the whole period of the sequence, results can be calculated and displayed with progressive averaging. Each run can be as short as 12 seconds (or shorter if required). An advantage of this technique is the ability to monitor the responses after each short run and to decide if the last run provides meaningful results and if more runs are required. This is accomplished by visual inspection, based on the experience of the operator and depends on, for example the clarity of the measurement signals and acceptably low level of noise. Another advantage is that increasing the number of stimulated segments does not increase the recording time required. For example, using the Gold sequence family for recording a pattern VEP, as many as 1025 segments of visual field can be stimulated simultaneously using a sequence of 1023 elements of code, requiring only 12 seconds of recording time The equivalent number of stimuli using the Sutter system would require 16 minutes of data recording before any results could be assessed.
The stimulus used can be a pattern or flash, and can therefore be adapted to multifocal electroretinogram (ERG) recording.
According to a first aspect of this invention there is provided a method of providing a visual reaction map of at least part of the visual field of an eye of a subject, the method comprising:
(a) presenting to said visual field a plurality of segments each of the segments comprising an individually activated image;
(b) changing each of said individually activated images in each of said segments according to a binary sequence each of said images being changed in a different way from all other of said images whereby the changing of one of said images does not substantially correlate with the changing of any of the other of said images;
(c) detecting measurement signals in said subject while said visual field is presented with said changing;
(d) correlating said measurement signals with each of the binary sequences used to activate each of said individual segments; and
(e) providing said visual reaction map from said correlating.
Generally the method further comprises
(f) determining from said visual reaction map whether said eye has one or more areas of defective vision.
According to a second aspect of this invention there is provided a system for providing a visual reaction map of at least part of the visual field of an eye of a subject, the system comprising:
(a) means for presenting to said visual field a plurality of segments each of the segments comprising an individually activated image;
(b) means for changing each of said individually activated images in each of said segments according to a binary sequence each of said images being changed in a different way from all other of said images whereby the changing of one of said images does not substantially correlate with the changing of any of the other of said images;
(c) means for detecting measurement signals in said subject while the visual field of the eye of said subject is presented with individually activated images in each of said segments which are changed according to a binary sequence each of said images being changed in a different way from all other of said images whereby the changing of one of said images does not substantially correlate with the changing of any of the other of said images;
(d) means for correlating said measurement signals with each of the binary sequences used to activate each of said images in said segments; and
(e) means for providing said visual reaction map from said correlating.
Suitably, the individually activated images are computer generated.
According to a third aspect of this invention there is provided a method for assessing extent of visual field loss in a patient suffering from a neuro-opthalmic disorder, comprising providing a visual reaction map in accordance with the method of the first aspect of this invention and assessing the extent of visual field loss from said visual reaction map.
The binary sequences may be, for example Gold, Kasami, Bent or the like. Any binary sequence which enables the changing of each of the individually activated images in each of the segments being changed in a different way from all other of the images whereby the changing of one of the images does not substantially correlate with the changing of any of the other images, may be employed. Preferably, the sequences are Gold and Kasami. Details of these sequences are set out in Table 1.
With regard to step (b) in both aspects of the invention set out above, the use of the different binary sequences for changing the image within each said segment which belongs to a family of sequences with acceptably low cross-correlation between members of said family and an impulse valued auto-correlation function confers a significant advantage for clinical application. Due to low cross-correlation between members of the said family there is practically no cross-talk between responses derived from stimulation of different areas of the visual field. This allows the stimulation of all parts of the tested visual field simultaneously with no time shift between the segments. Therefore, sequences as short as 127 elements of code (1.7 sec at 75 Hz frame rate) can be used. For practical purposes, the shortest sequence consists of 1023 elements of code which results in 13.6 sec of recording time at 75 Hz.
There is also no increase in recording time associated with increased number of areas of the visual field stimulated, which is due to the fact that the families of sequences have a large enough number of the members. For instance, the Gold family has 1025 members for the sequence of 1023 elements of code, which means that up to 1025 areas of the visual field can be stimulated simultaneously.
Each segment of the image is a pattern which is representative of the visual reaction of that pan of the eye that corresponds to that segment. The pattern may be a black and white pattern, and gray and black pattern, a color pattern or other suitable pattern e.g. a pattern reversal. The image in each segment may also produce a diffuse white illumination and may change in brightness. Each image in each segment may also be a diffuse color illumination and the sequences may produce a change in color.
Typically, the measurement signals are detected by means of electrodes which are placed on the head or eyelids of the subject. The measurement signals correspond to visually evoked potentials. These electrodes are placed thus by methods known in the art of ERG recording. The method of the invention usually involves placing electrodes on the head or eyelids of the subject and detecting the measurement signals via these electrodes.
The visual reaction map is any visual reaction map which suitably displays measurement signals generated by the above-described means. For example, the visual reaction map is suitably a Humphrey Visual Field Map. Generally the visual reaction map shows significant reduction in amplitude of visual reaction in areas of defective vision as compared to amplitude of visual reaction in areas of normal vision.
The intensity of the plurality of segments presented to the visual field is sufficient to result in detectable measurement signals but not of an intensity that would cause damage to the exposed eye of the subject The intensities used in practising this invention are well known in this art.
In practising the methods of this invention, it is possible to provide a visual reaction map using one run only. However, it is preferable that more than one run is carried out (e.g. 2, 3, 4, 5, 6, 7, 8, 9, 10 or more runs). As the number of runs increases, the runs are progressively averaged. The result of this progressive average is that as the number of runs increases, a visual reaction map is produced with decreasing levels of noise. Referring to the dicussion of U.S. Pat. No. 4,846,567(Sutter) above, that method requires long recording times and the person carrying out the test can only see the result of the test at the end of the recording time. The significance of the shorter recording times of this invention and the ability to carry out the test a number of times and average those results is that as mentioned, it is possible to carry out one run and it is possible to observe the results as the test is progressing and finally, even repeating the test a number of times still allows a shorter time of subjecting the patient to the test than the prior art methods such as those described in Sutter. Typically, six to eight runs may are performed, each run lasting approximately 12 seconds or less. The image is displayed on any suitable display that can present information derived from a suitable binary sequence (e.g. a monitor such as a computer monitor or screen onto which the image in projected, a hologram etc.)
When analyzing the measurement signals from the subject, a correlation between these measurement signals and the binary sequence used to activate the individual segment of the computer generated image is calculated to separate a response for that segment from other segment responses. As a result, a visual reaction map of the visual field is produced as a set of cross-correlation functions between the signal and the members of the family used to stimulate individual segments of the computer generated image. The map thus derived, is a representation of the vision of a subject in each part of the visual field.
For example, where a person is suffering from glaucoma, the results show reductions in areas of defective vision, known as scotomas. Detection and monitoring of scotomas is vital in the diagnosis and management of glaucoma and other neuro-ophthalmic disorders affecting the visual system.